The presence of low molecular weight low density lipoprotein (LDL) particles in plasma has been associated with premature coronary artery disease. In this study we have examined factors affecting LDL subfraction distribution as determined by 2% to 16% polyacrylamide-agarose gradient gel electrophoresis of whole plasma in a normal, primarily middle-aged, population of adult male and female participants (n = 280, ages 25 to 75 years) in the Framingham Offspring Study. Seven major LDL bands (LDL-1 to LDL-7) were observed in different individuals, with most subjects having either one or two major bands. The presence of low molecular weight LDL (LDL-4 to LDL-7) in plasma as the predominant LDL type was significantly more common in men than in women (43.5% versus 14.8%, p less than 0.001). The presence of low molecular weight LDL was correlated (p less than 0.01) with increased age, plasma triglyceride, total cholesterol, very low density lipoprotein (VLDL) cholesterol, LDL cholesterol (in women only), and apolipoprotein (apo) B concentrations, as well as with decreased high density lipoprotein (HDL) cholesterol and apo A-I levels. Approximately 69% of the variability in LDL subfractions could be accounted for by alterations in plasma triglyceride and HDL cholesterol levels. These data are consistent with the concept that LDL subfraction distribution is influenced by gender and plasma lipoprotein levels and can be determined readily by the use of whole plasma.